The purpose of this award is to provide the applicant with the opportunity to obtain the skills necessary to become a fully independent biomedical investigator with expertise in the application of molecular biological techniques to questions of the pathology of epithelial-mesenchymal interactions. With these skills, the applicant will apply his training towards research in craniofacial development and oral pathology while developing a career in academic dentistry. The initial phase of the award will be spent in didactic study within the interdisciplinary program in Cellular and Molecular Biology at the University of Michigan and in laboratory rotations learning different techniques of molecular biology (RFLP analysis, transgeneic mouse procedures, cloning technology, site directed mutagenesis, cDNA expression in mammalian cells, in-situ hybridization, immunolocalization of target proteins in embryologic tissues). The final phase will consist of application of these research tools to investigate the role of an extracellular, cell adhesion protein (thrombospondin) in odontogenesis. The aim of this research is to integrate the role of thrombospondin to the rapidly expanding knowledge available on cell adhesion proteins, other extracellular matrix proteins, and cellular transmembrane receptors in the epithelial-mesenchymal interactions occurring in tooth formation. Since tooth formation is a model to study the way genes regulate the spatial and temporal formation of organs dependent on the interaction of different embryonic cell lines, information obtained from this model should be applicable to the development (normal and aberrant) of other organ systems.